We carried out preliminary studies in intravenous drug users of laboratory markers proposed as surrogate measures of efficacy in clinical trials. We found (a) very low rates of p24 antigen detectability in HIV-infected black women, but not black men, and (b) significantly lower serum beta-2 microglobulin levels in black than in white drug users. These differences were not compatible with observed CD4 lymphocyte counts, and there were no gender or ethnic differences in HIV negative controls. These results suggest difficulties in the use of these markers or in clinical trials. We will examine these suggestive results further in a study of male-female and blackwhite differences in surrogate markers: (a) We will examine p24 and serum Beta-2 microglobulin levels cross- sectionally in a large serological study of intravenous drug users and partners in order to confirm the results and to examine whether differences in laboratory markers can be explained by risk factors such as drug use or drug treatment, STD serology and reproductive history. (b) We will examine p24 and serum Beta-2 microglobulin levels and in addition CD4 lymphocyte counts in 250 HIV-infected intravenous drug users currently in followup. In this study we will explore the relationship of the serum markers and CD4 lymphocyte counts, will examine changes in these three markers prospectively, and will determine whether they can be explained by current methadone use, current drug use, or anti-HIV therapy.